Purpose To evaluate the relative bioavailability of a domestic sustained-release metformin tablets (SRM) compared against an immediate-release metformin tablets (IRM) using a multiple-dose,two-way crossover design after a single-dose study. Methods Eighteen healthy adult male volunteers,aged 18 to 22 years (mean,20 years),weighing 55 to 76 kg (mean,64 kg) and with height ranging from 166 to 180 cm (mean,173 cm),and blood glucose levels from 4.0 to 5.9 mmol/L (mean,4.3 mmol/L) participated in the study.The concentrations of metformin in plasma were determined using a ion-pair liquid chromatographic method. Results In single-dose study,the mean residence time (MRT),Tmax,and apparent elimination half-life (T1/2) for SRM were significantly longer and Cmax significantly lower than the corresponding values determined for IRM.The similar results were also demonstrated in multiple-dose study.The mean values of the relative bioavaibility of SRM compared with IRM in two administration ways were (85.95±0.97)% and (86.44±7.88)%,respectively.The single-dose and multiple-dose administration of the 90% confidence interval for the ratio of the logarithmic transformed AUC values of SRM over those of IRM were calculated to lie between 0.83 and 0.88,0.83 and 0.89,respectively,being within the acceptable bioequivalence limit of 0.80～1.25. Conclusion SRM was of the characteristic of sustained-release pharmacokinetics.The relative bioavailability for single dosing was similar to that of multiple dosing,and both of the administration ways demonstrated bioequivalence in absorption between SRM and IRM.

Objective To investigate the effect of hypertension on the large artery elasticity index (C1),the small artery elasticity index (C2) and the medial structure of the ascending aorta as well as the relationship between artery elasticity and the medial structure of the ascending aorta.Methods Sixty patients with CHD receiving coronary artery bypass graft surgery at our hospital were divided into two groups:30 patients in the hypertension group and 30 patients in the non-hypertension group.C1 and C2 were measured using the CVProfilor DO-2020 system.Sections of tissues taken from the anterior wall of the ascending aorta during the surgery were subjected to Masson's trichrome staining for the detection of vascular smooth muscle and collagen fibers and Weigert's resorcin-fuchsin staining for the detection of elastic fibers.The relative areas of vascular smooth muscle fibers,collagen fibers and elastic fibers of the ascending aorta were measured by a computer image analysis system under the light microscope.The linear correlations of C1 and C2 with the medial structure of the ascending aorta were analyzed.Results C1 in the non hypertension group was higher than that in thehypertensiongroup[11.9±1.8 (ml/mmHg×10) w 13.1±2.5 (ml/mmHg×10),t 2.22,P ＜0.05].In the media of the ascending aorta,the relative content of collagen fibers was higher,while the relative content of elastic fibers was lower in the hypertension group than in the non-hypertension group [(46.0±3.8)％ w (42.2±3.0)％,(17.5±3.5)％ vs.(19.3 2.7)％,respectively,t=4.24 and 2.20,P＜0.01 or 0.05].C1 was positively correlated with the relative content of elastic fibers but negatively correlated with the relative content of collagen fibers in both groups (r=0.52 and 0.39,respectively,P＜0.05 or 0.01).Conclusions The main pathogenic basis of hypertension-induced decline in arterial elasticity in CHD patients is increased collagen fibers and reduced elastic fibers with disorganization of the two types of components.C1 may accurately reflect the effect of hypertension on medial collagen fibers and elastic fibers in the ascending aorta.

Objective To observe the expression of tumor stem cell markers P 75NTR,Oct-4,Sox-2,Lin28 and Nanog in the tumor sphere from esophageal squamous cells carcinoma Eca 109 and identify the esophageal squamous cell cancer stem cell marker .Methods The serum-free culture method was used for generating tumor spheres: proliferation was observed in enrichment culture tumor spheres .Small tumor spheres were obtained after 5 days culture and big and round tumor spheres appeared after 14 days culture which were collected for experiments and passaged .The expression and location of P75NTR,Oct-4,Sox-2,Lin28, and Nanog were detected by immunofluorescence cytochemistry .Results The expressions of P75NTR,Oct-4 and Lin28 were positive in the center of tumor spheres and some on cytoplasm and other in nuclei of Eca109 monolayer cells.However, Oct-4 fluorescence intensity was weaker than P75NTR.The expressions of Sox-2 and Nanog were positive in cytoplasm of tumor spheres and Eca 109 monolayer cells .Conclusion The cells expressing P75NTR, Oct-4, and Lin28 in the center of the tumor sphere may be esophageal cancer stem cells .

Objective To investigate the pathogen characteristics of perforated appendicitis in children and the perioperative use of antimicrobials in order to provide evidence for the rational use of perioperative antibiotics. Methods The perioperative usage of antibiotics was analyzed to determine the reasonableness of antimicrobial use in children with perforated appendicitis who were discharged from July 2011 to August 2014,based on“guidelines of clinical use of antibiotics”and results of bacterial culture. Results Inflammatory secretions obtained from 126 children(126/ 149)were sent for examination and the examination rate was 84.56%.A total of 117 cases were found positive for cultured pathogens,and the detection positive rate was 92.86%.Three types of bacteria ranking the first three places were Escherichia coli,Pseudomonas aeruginosa and CitroBacter freundii.The utilization rate of antibacterial agents was 100.00%,with a dominant use of cephalosporins and nitrate imidazoles. Rational use of antimicrobial agents was found in 144 cases(accounting for 96.64%). Conclusion The major pathogen in perforated appendicitis is still Escherichia coli,which is highly sensitive to commonly used antibiotics,and drug-sensitivity testing results can help guide the treatment programs and antibiotics selection.

Objective:To investigate the off-label drug use in the outpatients of Zhengzhou children's hospital in 2013 to provide the evidence for improving the rational drug use in pediatrics. Methods:The prescriptions of outpatients were randomly selected from January to December in 2013. According to the drug instruction, the off-label drug uses were analyzed in the following aspects: sam-pling conditions, the kinds of off-label drug use, the incidence of off-label drug use in different age groups and drug categories. Re-sults:A total of 8 684 prescriptions with 16 344 medical records involving 410 kinds of drugs were analyzed, and the rate of off-label drug use was 70. 87% for prescription, 51. 21% for medical orders and 71. 95% for category, respectively. The primary types of off-label drug use were over applicable people (50. 83%), dosage(21. 00%) and frequency (19. 04%). The top 3 age groups with high-est off-label drug use rate were neonates (63. 27%), infants (56. 20%) and school-age (44. 98%). The top 5 drugs with highest off-label drug use rate were cardiovascular system medicines (99. 02%), anti-infective agents (64. 14%), vitamin and mineral drugs (62. 89%), hematological system medicines (59. 48%) and Chinese patent drugs (53. 43%). Conclusion: Off-label drug use in outpatients is prevalent. Physicians should master indications, usage and dosage described in instructions, select suitable dosage form, reduce off-label drug use and improve drug safety in pediatrics.

Objective To investigate therapeutic effects of phlorizin on the early stage of diabetic retinopathy(DR)in diabetic db/db mice.Methods The 24 db/db male mice were divided into 3 groups of phlorizin-treated diabetic group(20mg/kg of phlorizin by intragastric gavage)(DMT,n =8),diabetic group(normal saline solution by intragastric gavage)(DM,n=8),with C57BLKS/J db/ m mice as the control group(CC,n=8)for ten weeks.After ten weeks,all mice were sacrificed and the retina was isolated.The specimen was embedded in paraffin wax and sliced.The sections were dyed with Sudan red and observed for retinal morphological change.Meanwhile,the expressions of GSK-3β and phospho-GSK-3β in retinas were determined by western blot.Results During the study,the CC group showed good condition.The DM group featured with polydipsia,polyphagia and a rapid increase of body weight.Phlorizin-treated diabetic mice displayed much better than the DM group.Compared with CC group,DM group showed cells proliferation in capillary endothelia and obvious thickening in basement membrane.After administration of phlorizin,the vascular lesion of central regions was remarkably improved.The expression level of phospho-GSK-3β protein was lower in DM group than in control group(76.2±15.8 vs.255.4 ± 10.7,t =16.30,P＜0.01)and was higher in Phlorizin-treated DM group(188.5±18.4)than in DM group(76.2± 15.8,t=8.05,P＜0.01).Conclusions Phlorizin decreases phospho-GSK-3β3expression in retina in db/db diabetic mice and suppresses the GSK-3βactivity,which leads to the protection of DR.

OBJECTIVE:To provide baseline data for the formulation of the strategy for medical institutions in China. METH-ODS:3 600 discharged medical records were randomly collected from our hospital in 2013. According to drug package inserts,the judgment was carried out about whether off-label drug use existed in medical orders. The types of off-label drug use,off-label drug use of children in different age groups and of various drugs were all analyzed. RESULTS:A total of 3 268 hospitalized children were includ-ed,and 35 523 medical orders were analyzed,involving 468 types. Based on children,medical orders and drug types,the incidence of off-label drug use were 91.34%,35.72%and 48.72%,respectively. The types of off-label drug use mainly included pediatric medica-tion information(74.21%), exceeding route of administration(8.12%)and overage(8.45%). The top 3 age groups with respect to the incidence of off-label drug use were adolescents(42.42%),neonate(37.97%)and infant(35.48%). Top 4 drugs of off-label use in the list of medical orders were anti-infective drugs(23.65%),electrolytic,drugs for acid-base balance and nutrition(12.21%), drugs for respiratory system(36.84%)and cardiovascular drugs(63.21%). CONCLUSIONS:The off-label drug use of hospitalized children is common in our hospital. It is urgent to develop related laws and regulations or guidelines to regulate off-label drug use in or-der to ensure the safety of pediatric drug use.

Objective To compare the clinical effect of vascularized fibular flap transplantation and vancomycin sulfate calcium on chronic osteomyelitis of the tibia and bone defects.Methods A total of 35 cases with chronic tibial osteomyelitis and bone defect were involved and divided into group A with 21 cases receiving anastomosis of vascularized fibular flap transplantation and group B with 14 cases recciving vancomycin sulfate calcium.Infection control rate and Enneking score were compared in both groups.Simultaneous detection of two groups preoperative,postoperative 2 weeks,1 month and 3 months of the levels of CRP and PCT were conducted.Results Postoperative CRP and PCT were under control in both groups.No statistical significance was found in the comparison of CRP and PCT preoperative and postoperative 2 weeks,1 month and 3 months.In terms of infection control rate,two groups had no signiticant difference (P ＞ 0.05) and there was statistical significance of the comparison of postoperative Enneking score (P ＜ 0.05).Conclusions The clinical results of the two methods are satisfied.The infection degree and the length of the bone defect are decisive factors in choosing the treatment method and sometimes the combination of two treatment methods may be a better choice.

Objective To observe the effect of rotavirus (RV) infection on expression level and bioactivity of Na+-H+ exchanger 3 (NHE3) in Caco-2 cells. Methods Model of NHE3-expressing Caco-2 cells was constructed and studied in terms of intervention: control, RV, clathrin antagonist chlorpromazine (CPZ), and CPZ + RV. NHE3 activity and NHE3 protein amount on cell surface were determined by BCECF-AM and biotinylation, respectively. Expression level of clathrin was assayed by Western blot. Results Compared with control group, NHE3 activity and NHE3 surface protein level significantly decreased when the cells were treated with RV. These effects could not be completely cancelled by clathrin antagonist CPZ. Moreover, RV treatment could increase cellular protein level of clathrin, which was cancelled by CPZ. Conclusions The effect of RV infection on NHE3 expression level and biological activity may be related to clathrin-dependent endocytosis pathway, and may be also affected by other endocytosis pathways.

Objective ToanalyzetheCTfeaturesandthediagnosticvalueofpulmonarychondroma.Methods Tencasesofpulmonary chondromaprovenbypathologywereretrospectivelyanalysed.Thenumber,location,size,shape,margin,calcificationpatternandCT valueofthelesions wereanalysedonnonGenhancedandenhanced CTscans.Results Allthe10casesofpulmonarychondroma showedsolitary,mildlylobulated,wellGcircumscribed masses.6lesionswerelocatedintherightlung,and4lesionswereintheleft lung.Thesizeofthelesionsrangedform1.3cm×0.8cmto10.7cm×9.8cm.OnplainCTimages,9lesions(90%)showedvaried calcification,withpunctatecalcificationin8lesionsandringcalcificationin1lesion.OncontrastGenhanced CTimages,6lesions showedslighthomogeneousenhancement(enhancedvalue≤14HU).Conclusion Pulmonarychondromaisusuallylocatedintheperiphery ofthelung.Thenodulehasasmoothboundary,withsignificantcalcificationandslightlyenhancement,whichcouldbehelpfulindiagnosis ofthedisease.